Salmonella causes grave systemic infections in humans and other animals and provides a paradigm for other diseases where the bacteria have both intracellular and extracellular lifestyles. New generations of vaccines rely on the essential contribution of the antibody responses for their protection. The quality, antigen specificity and functions associated with antibody responses to this pathogen have been elusive for a long time. Recent approaches that combine studies in humans and genetically manipulated experimental models, and exploit awareness of the location and within-host life cycle of the pathogen, are shedding light on how humoral immunity to Salmonella operates. However, this area of research remains full of controversy and discrepancies.